Blood has properties of being activated and thrombus being formed therein when it is brought into contact with foreign matter. If thrombus is formed in a circuit or dialyzer in an extracorporeal circulation of blood such as an artificial kidney, circulating pressure rises and in addition to becoming impossible for blood to circulate shortly, there is a risk of the blood vessel being obstructed if a portion of generated thrombus enters the body. Therefore, it is necessary to add a blood anticoagulation activity (anti-coagulability) substance and this is a method widely used. Inexpensive heparin is generally used as the anti-coagulability substance. However, heparin cannot be used for patients of heparin-induced thrombocytopenia (hereinafter, referred to as HIT) and patients with bleeding such as those immediately after an operation and an expensive anticoagulant such as nafamostat mesilate and gabexate mesilate needs to be used instead, leading to a problem of rising medical expenses (See Non-patent Documents 1, 2, and 3).
Research on anti-coagulability materials that can reduce usage of anticoagulants by imparting anti-coagulability to the surface of material or can be used under conditions of no added anticoagulant has been conducted. That is, such materials are obtained by immobilizing anti-coagulable substances on the surface of material and include a heparinized material as the most researched material. The main method of immobilizing heparin to a material is based on an ionic bond using cations of ammonium salt and the like introduced into the material and anions of heparin (See Non-patent Document 4). However, in this case, heparin is likely to elute and thus, this method cannot be used for patients with HIT and also has a problem of lowered anti-coagulability. Therefore, several methods of immobilizing heparin based on a covalent bond have been reported to resolve the problem of elution. First, an immobilization method based on the covalent bond formed organic chemically has been reported, but has a problem of lowering anti-coagulability during chemical reaction (See Patent Document 1). Second, a method of immobilizing heparin on a material based on the covalent bond while preventing anti-coagulability from being lowered by using an ion beam and laser light has been reported, but since an ion beam and laser light are used, it is difficult to immobilize heparin in a portion such as the surface inside a hollow fiber where a shadow is cast by an ion beam (See Patent Document 2).
Heparin itself has very low anti-coagulability and expresses high anti-coagulability by being bound to antithrombin III (hereinafter, referred to as ATIII). That is, there is also a problem that anti-coagulability is insufficient in ATIII deficient blood (See Non-patent Document 2).
With respect to the above problems of heparin immobilization material, research on materials on which compounds having anti-coagulability other than heparin are immobilized has been conducted (See Patent Document 3). However, there is a problem that it is difficult to suppress platelet attachment by a compound having anti-coagulability alone, leading to formation of platelet thrombosis. In addition, no proposal has been made regarding the problem of elution of a compound having anti-coagulability from substrate.
In recent years, research on immobilization of a compound having anti-coagulability other than heparin by radiation has been conducted (See Patent Document 4). By using this method, a lowering of anti-coagulability with radiation irradiation can be suppressed and further, elution of the compound having anti-coagulability from the substrate can be said to be reduced to a certain extent. However, according to the method of immobilizing only the compound having anti-coagulability, an intrinsic blood-clotting reaction can be suppressed, but it is difficult to suppress platelet attachment so that a sufficient level of anti-coagulability has not yet been achieved. Moreover, non-reactants during radiation irradiation are not taken into account here and the lowering of elution of the compound having anti-coagulability from the substrate cannot have been reduced.    Patent Literature 1: JP-A-H2003-507082    Patent Literature 2: JP-A-H2001-213984    Patent Literature 3: JP-A-H2004-525888    Patent Literature 4: JP-A-H2006-291193    Non-Patent Literature 1: Kazuo Ota, “Jinkoujinzounojissai (in revised form 4)”, Nankodo, 1993, pp 158-164    Non-Patent Literature 2: Tetsuzo Agishi et al. “Tousekinyumon”, Syujunsha, 1994, pp. 170-182    Non-Patent Literature 3: American journal of hematology. 2006 81 (1), pp. 36-44    Non-Patent Literature 4: Journal Biomedical Materials Research. 1998 39, pp. 86-91